rs201728852
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The ENST00000375499.8(SDHB):c.700C>T(p.Leu234=) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,614,030 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. L234L) has been classified as Likely benign.
Frequency
Consequence
ENST00000375499.8 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SDHB | NM_003000.3 | c.700C>T | p.Leu234= | synonymous_variant | 7/8 | ENST00000375499.8 | NP_002991.2 | |
SDHB | NM_001407361.1 | c.646C>T | p.Leu216= | synonymous_variant | 7/8 | NP_001394290.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SDHB | ENST00000375499.8 | c.700C>T | p.Leu234= | synonymous_variant | 7/8 | 1 | NM_003000.3 | ENSP00000364649 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000135 AC: 34AN: 251432Hom.: 0 AF XY: 0.000169 AC XY: 23AN XY: 135892
GnomAD4 exome AF: 0.0000739 AC: 108AN: 1461762Hom.: 1 Cov.: 31 AF XY: 0.000106 AC XY: 77AN XY: 727194
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74464
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 02, 2022 | In silico analysis supports that this variant does not alter splicing; Identified in individuals with pheochromocytoma or paraganglioma (Ben Aim et al., 2019); Also known as p.L206=; This variant is associated with the following publications: (PMID: 30877234) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2022 | - - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | May 17, 2021 | - - |
Hereditary pheochromocytoma-paraganglioma Benign:2
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Dec 13, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Pheochromocytoma;C0238198:Gastrointestinal stromal tumor;C1861848:Paragangliomas 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 27, 2023 | - - |
Paragangliomas 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Carney-Stratakis syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at